When a 53-year-old man asked Dutch doctors to treat his obsessive-compulsive disorder (OCD) several years back, they suggested a new but promising surgical treatment: implanted electrodes that would stimulate deep brain tissue involved in decision-making, reward-seeking, and motivation. The treatment apparently helped him go off one of his psychiatric medications, but it came with a surprising side effect—it also seemed to improve his type 2 diabetes. Now, researchers think they know why. A new study suggests that a boost in the activity of dopamine, a neurotransmitter involved in motivation and pleasure, improves the body’s ability to process sugar.
This is the first time such a pathway, previously seen in mice, has been found in humans, says Mike Michaelides, a neuroscientist at the National Institute on Drug Abuse in Baltimore, Maryland, who was not involved in the new research. That doesn’t make deep brain stimulation (DBS) realistic for most people with diabetes, but other, less invasive brain therapies that target dopamine might one day be feasible.
Diabetes occurs when glucose, or sugar, in a person’s bloodstream remains in chronically high concentrations. Type 1, which typically begins in childhood, results when the immune system destroys the pancreatic cells that make insulin, the hormone that lets our cells use sugar as food. Type 2 diabetes, typically triggered by a combination of bad genes, poor eating habits, and a lack of exercise, also damages the body’s ability to produce its own insulin. As time goes on, cells are hard-pressed to remove sugar from the blood, and people require larger and larger amounts of insulin to keep their blood sugar stable. There is no cure for either disease.
To test whether DBS was responsible for the man’s improvement (he went from injecting 226 international units of insulin per day to just 180), Mireille Serlie, an endocrinologist at the Academic Medical Center in Amsterdam, and colleagues recruited him for an experiment. Fourteen other men and women with DBS implants for OCD—but without diabetes—joined him. Serlie and colleagues turned off the DBS devices for 17 hours and measured participants’ fasting blood sugar levels and responses to insulin. DBS significantly increased insulin sensitivity in all participants, the team reports today in Science Translational Medicine.
Studies in mice have shown that dopamine released by neurons in the same general decision-making region they stimulated—called the ventral striatum—plays a key role in regulating glucose throughout the body. To see whether a similar mechanism exists in humans, her team gave 10 healthy men a drug that depletes dopamine levels. The men’s insulin sensitivity decreased in concert, bolstering the connection, they report.
The team also used optogenetics, which deploys lasers to control living cells, to stimulate striatal neurons in mice. As the neural cells released more dopamine, the rate at which other cells absorbed glucose from the rodents’ blood picked up. Michaelides says the mouse study confirms previous research by his group and other labs, suggesting that dopamine signaling in the nucleus accumbens—part of the ventral striatum—plays a key role in glucose metabolism.
Nima Saeidi, an assistant professor of surgery at Harvard Medical School in Boston, cautions that targeting dopamine in the brain through DBS or other methods may not be a useful treatment for most people with diabetes, because prolonged exposure to elevated levels of glucose and insulin profoundly alters the function of cells and organs. “It is very possible that the results the authors described here are not translatable to diabetic patients,” he warns. Serlie agrees that for some people, the damage to cells may be irreversible. But at earlier stages of the disease, she suggests, “it could really help” increase the effectiveness of the insulin people already produce.